肿瘤相关的免疫细胞在癌症进程中起着至关重要的作用。例如，来源于髓系的抑制性细胞（MDSCs）是不成熟的先天免疫细胞，它们渗透到肿瘤中发挥免疫抑制作用，并保护癌细胞免受宿主免疫系统和/或癌特异性免疫治疗的攻击。虽然肿瘤相关免疫细胞被认为是有希望的治疗靶点，但由于缺乏有针对性地作用于肿瘤区域内的免疫细胞群体并有效消除"保护性"免疫细胞和/或促进"抗肿瘤"表型的方法，抵抗肿瘤微环境中的免疫抑制仍然存在困难。 在这里，我们报告了一种新颖的基于纳米技术的方法，以作用于肿瘤相关免疫细胞并促进在乳腺癌小鼠模型中的"抗肿瘤"反应。利用ICAM-1配体装饰的、负载有miR-146a和Glut1的工程化胞外囊泡（EVs）通过体内体外生物合成，并每周一次至多连续5周内给予肿瘤带瘤小鼠。通过RT-qPCR、流式细胞术和组织学评估了这种治疗方式对免疫细胞群体和肿瘤进展的影响。我们的结果表明，与无荷载的ICAM-1装饰EVs相比，工程化EVs（即装饰有ICAM-1，并负载miR-146a和Glut1）的每周给予可阻碍肿瘤进展。对肿瘤的流式细胞学分析表明，免疫细胞群体的表型发生转变，向更具促炎状态转化，并有助于肿瘤靶向性T细胞的浸润，这与肿瘤大小的减小和转移负担的减轻相关。总体而言，我们的结果表明，装饰ICAM-1的EVs可作为有力的纳米技术平台，用于免疫细胞靶向治疗实体瘤。

Tumor-associated immune cells play a crucial role in cancer progression. Myeloid-derived suppressor cells (MDSCs), for example, are immature innate immune cells that infiltrate the tumor to exert immunosuppressive activity and protect cancer cells from the host's immune system and/or cancer-specific immunotherapies. While tumor-associated immune cells have emerged as a promising therapeutic target, efforts to counter immunosuppression within the tumor niche have been hampered by the lack of approaches that selectively target the immune cell compartment of the tumor, to effectively eliminate "tumor-protecting" immune cells and/or drive an "anti-tumor" phenotype. Here we report on a novel nanotechnology-based approach to target tumor-associated immune cells and promote "anti-tumor" responses in a murine model of breast cancer. Engineered extracellular vesicles (EVs) decorated with ICAM-1 ligands and loaded with miR-146a and Glut1, were biosynthesized (in vitro or in vivo) and administered to tumor-bearing mice once a week for up to 5 weeks. The impact of this treatment modality on the immune cell compartment and tumor progression was evaluated via RT-qPCR, flow cytometry, and histology. Our results indicate that weekly administration of the engineered EVs (i.e., ICAM-1-decorated and loaded with miR-146a and Glut1) hampered tumor progression compared to ICAM-1-decorated EVs with no cargo. Flow cytometry analyses of the tumors indicated a shift in the phenotype of the immune cell population toward a more pro-inflammatory state, which appeared to have facilitated the infiltration of tumor-targeting T cells, and was associated with a reduction in tumor size and decreased metastatic burden. Altogether, our results indicate that ICAM-1-decorated EVs could be a powerful platform nanotechnology for the deployment of immune cell-targeting therapies to solid tumors.